Galantamine for Cognitive Deficits in Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- 1. Change on selected cognitive deficits associated with schizophrenia (e.g., spatial working memory, sustained attention and prepulse inhibition.)
研究概览
简要总结
The purpose of this study is to determine the acute effects of the nicotinic receptor allosteric modulator galantamine (0, 4 and 8 mg) on neurocognitive function in schizophrenic smokers (n=20) versus schizophrenic nonsmokers (n=10) in an outpatient human laboratory setting.
详细描述
The proposed study will entail a comprehensive evaluation of the effects of acute doses of the nAChR allosteric modulator galantamine hydrochloride (0, 4 and 8 mg) on neurocognitive measures in schizophrenic smokers (n=20) and schizophrenic non-smokers (n=10) in a human laboratory paradigm. After training on a battery of neurocognitive assessments, all subjects will be studied during three separate test weeks where they will complete the neurocognitive batter at baseline, and then again after acute administration of the three doses of galantamine in a counterbalanced order across subjects in each experimental group. Specifically, smokers would be randomized into one of two groups: 1) those who undergo overnight smoking abstinence prior to the study cognitive sessions in order to determine galantamine's effects on abstinence-induced cognitive impairment, and 2) those who may smoke as usual prior to the study cognitive sessions. The inclusion of nonsmokers will allow for the assessment of galantamine's effects on cognitive deficits in schizophrenia independent of cigarette smoking. Finally, genetic variations in key metabolic genes involved in catecholamine metabolism (COMT and DBH) would be evaluated as determinants of galantamine-related improvements in cognitive performance in schizophrenic smokers and nonsmokers.
We predict that galantamine will dose-dependently improve selected cognitive deficits associated with schizophrenia (e.g., spatial working memory, sustained attention and prepulse inhibition) which we have previously shown are selectively improved by cigarette smoking in smokers with schizophrenia [18], and that this effect would be more pronounced in nonsmokers with schizophrenia. If our results are positive, they would support the rationale for controlled clinical trials using nAChR agonists like galantamine to treat selected domains of cognitive dysfunction in this disorder.
Study Design:
The following experimental groups will be studied:
- Schizophrenic Smokers under abstinence conditions (n=10)
- Schizophrenic Smokers in the smoking condition. (n=10)
- Schizophrenic Nonsmokers (n=10)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Schizophrenic smokers (n=20) and schizophrenic nonsmokers (n=10) in these studies (total n=20 subjects) will be:
- •Between 18 and 60 years of age,
- •Have a Full Scale IQ score >
- •Smokers will meet DSM-IV criteria for nicotine dependence, and smoke at least 15 cigarettes per day, with an FTND score at baseline >5, breath CO >10, and plasma cotinine >150 ng/ml.
- •Nonsmokers will report a history of never smoking (<100 cigarettes lifetime) or be abstinent from smoking for at least 6 months prior to randomization, with abstinence biochemically confirmed by CO level <10 ppm and plasma cotinine <15 ng/ml.
- •Schizophrenic subjects will meet DSM-IV criteria for schizophrenia or schizoaffective disorder, and be on a stable dose of antipsychotic medication for at least three months, with positive symptoms stability as judged by the investigator.
- •Subjects must be non-treatment seeking smokers with respect to their nicotine dependence.
排除标准
- •Meet criteria for current abuse or dependence for any other alcohol or substance of abuse within the past 6 months, with the exception of nicotine dependence (smokers) or caffeine (all groups).
- •An inability to learn the neuropsychological tasks during the training session.
- •History of dementia, other neurological illness (e.g. idiopathic Parkinson's Disease, Epilepsy), or any other acute or chronic medical condition known to significantly influence neurocognitive function, at the discretion of the P.I. and Project Director.
- •A history of severe renal or hepatic insufficiency, or a known hypersensitivity to galantamine hydrochloride (Razadyne®).
- •For smokers, current use of any tobacco products (chewing tobacco, cigars, nicotine replacement therapies like lozenges, gum, nasal spray, inhaler or patch) besides cigarettes.
- •A history of hypotension, or currently taking anti-hypertensive medication.
- •Interested in quitting smoking (in which case they will be referred to our smoking cessation treatment study).
- •Not capable of giving informed consent for participation in this study.
- •Positive urine toxicology screen for any substance of abuse.
- •Patients who are pregnant or planning on becoming pregnant.
结局指标
主要结局
1. Change on selected cognitive deficits associated with schizophrenia (e.g., spatial working memory, sustained attention and prepulse inhibition.)
次要结局
未报告次要终点